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      Real-time computed tomography fluoroscopy-guided solitary lung tumor model in a rabbit

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          Abstract

          Preclinical studies of lung cancer require suitable large-animal models to allow evaluation and development of surgical and interventional techniques. We assessed the feasibility and safety of a novel rabbit lung cancer model of solitary tumors, in which real-time computed tomography fluoroscopy is used to guide inoculation of VX2 carcinoma single-cell suspensions. Thirty-eight rabbits were divided into four groups according to the volume of the VX2 tissue or cell suspension, the volume of lipiodol, the volume of Matrigel, and the injection needle size. The mixtures were percutaneously injected into rabbit lungs under real-time computed tomography fluoroscopy guidance. Two weeks later, VX2 lung carcinomas were confirmed via positron emission tomography/computed tomography, necropsy, and histology. Real-time computed tomography fluoroscopy allowed the precise inoculation of the tumor cell suspensions containing lipiodol, while the use of Matrigel and a small needle prevented leakage of the suspensions into the lung parenchyma. Solitary lung tumors were successfully established in rabbits (n = 22) inoculated with single-cell suspensions (150 μL), lipiodol (150 μL), and Matrigel (150 μL) using a 26-gauge needle. This combination was determined to be optimal. Pneumothorax was observed in only two of the 38 rabbits (5.3%), both of which survived to the end of the study without any intervention. Real-time computed tomography fluoroscopy-guided inoculation of VX2 single-cell suspensions with lipiodol and Matrigel using a small needle is an easy and safe method to establish solitary lung tumors in rabbits.

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          The IASLC Lung Cancer Staging Project: Proposals for the Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer.

          An international database was collected to inform the 8 edition of the anatomic classification of lung cancer. The present analyses concern its primary tumor (T) component.
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            Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase.

            The rabbit VX2 tumor when implanted in the liver has proven convenient as a model for studying hepatocellular carcinomas. However, its metabolic properties have not been well studied. Significantly, studies described here show that the VX2 tumor exhibits a high glycolytic/high hexokinase phenotype that is retained following implantation and growth in rabbit liver. In addition, results of a limited screen show that the glycolytic rate is inhibited best by 2-deoxyglucose (2DOG) and 3-bromopyruvate (3BrPA), the former compound of which is phosphorylated by hexokinase but not further metabolized, while the latter directly inhibits hexokinase. Finally, when tested on hepatoma cells in culture both inhibitors facilitated cell death. These studies underscore the usefulness of the VX2 tumor model for the study of advanced liver cancer and for selecting anti-hepatoma agents.
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              Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.

              More than 80,000 people undergo resection of a pulmonary tumor each year, and the only method to determine if the tumor is malignant is histologic analysis. We propose that a targeted molecular contrast agent could bind lung adenocarcinomas, which could be identified using real-time optical imaging at the time of surgery.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 June 2017
                2017
                : 12
                : 6
                : e0179220
                Affiliations
                [1 ]Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea
                [2 ]Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Korea
                [3 ]Department of Radiology, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Korea
                [4 ]Department of Nuclear Medicine, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Korea
                Central South University, The Third Xiang Ya Hospital, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: B.H. Choi, H.S. Young, H.K. Kim, Y.H. Quan.

                • Data curation: BHC YHQ HKK JSE HSY.

                • Formal analysis: BHC HKK JSE HSY.

                • Funding acquisition: HKK.

                • Investigation: BHC YHQ HKK JSE HSY JYR KNH YHC.

                • Methodology: BHC YHQ HKK HSY.

                • Project administration: BHC YHQ HKK JSE HSY.

                • Resources: BHC YHQ HKK JSE HSY.

                • Software: HSY JSE.

                • Supervision: HKK.

                • Validation: BHC.

                • Visualization: BHC HKK JSE HSY.

                • Writing – original draft: BHC HKK HSY.

                • Writing – review & editing: HKK.

                Author information
                http://orcid.org/0000-0001-7604-4729
                Article
                PONE-D-16-44201
                10.1371/journal.pone.0179220
                5469482
                28609443
                7ca3f8e4-e905-4cc0-92af-9833bdab18c4
                © 2017 Choi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 November 2016
                : 25 May 2017
                Page count
                Figures: 4, Tables: 2, Pages: 11
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: NRF-2015R1A2A2A04005760
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003710, Korea Health Industry Development Institute;
                Award ID: A121074
                Award Recipient :
                This work was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (No: A121074), a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (NFR-2015R1A2A2A04005760). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Lung and Intrathoracic Tumors
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Rabbits
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Rabbits
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Lung and Intrathoracic Tumors
                Secondary Lung Tumors
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Computed Axial Tomography
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Computed Axial Tomography
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Tomography
                Computed Axial Tomography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Tomography
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                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Tomography
                Computed Axial Tomography
                Biology and Life Sciences
                Anatomy
                Thorax
                Pleural Cavity
                Medicine and Health Sciences
                Anatomy
                Thorax
                Pleural Cavity
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Pulmonary Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Pulmonary Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Pulmonary Imaging
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Surgical Oncology
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Surgical Oncology
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                Oncology
                Clinical Oncology
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                Medicine and Health Sciences
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